Human rhinoviruses (HRV) are particular picornaviruses and are the most common infectious viral agents of the respiratory system. Indeed, they are the primary cause of the “common cold”. The virus particles consist of a modular protein shell (the capsid) which encloses a short single strand of RNA.
One particular anti-picornavirus compound, which functions as a capsid-binding inhibitor and has been the subject of recent human clinical trials, is 4-[2-[1-(6-methyl-3-pyridazinyl)-4-piperidinyl]-ethoxy]benzoate—otherwise known as “Pirodavir”. Pirodavir, being lipophilic, displays poor aqueous solubility and is often formulated with a cyclodextrin host. The resultant complex is more soluble in aqueous media, and allows delivery of the drug through such means as a nasal spray. It has, however, been shown that facile endogenous cleavage of the ester moiety in pirodavir leads to poor bioavailability of the molecule regardless of the chosen excipient. Furthermore, and in addition to cost, cyclodextrin host molecules have been shown to be otherwise disadvantageous in the formulation of pharmaceuticals (Int. J. Pharm., 2002, 246, 25-35). Another promising anti-picornavirus compound, “Pleconaril”, has been shown to interact adversely with patients using oral contraceptive formulations.
Clearly there is a need for an anti-picornavirus compound which displays desirable aqueous solubility properties, is stable under physiological conditions and has few adverse interactions. Additionally it is desirable that such a compound would be relatively easy to form and would be stable on storage in solid and solution form.